Cancer Signaling and Experimental Therapeutics Research in the Cancer Signaling and Experimental Therapeutics (CSET) Program focuses cell signaling pathways and how they impact cancer progression and therapy. The overall goal of the members of this program is to elucidate basic signaling mechanisms relevant to tumor biology and apply this knowledge to the discovery and development of new therapeutic approaches. There are two major overiapping themes within the Program's research: The first theme is Cancer Signaling and is comprised of three interrelated research areas;GTPases and kinases, hormonal signaling and cell adhesion signaling. The second theme is Experimental Therapeutics and is comprised of three interrelated research areas;drug delivery and RNA interference, small molecules and clinical trials. Major accomplishments of the Cancer Signaling and Experimental Therapeutics Program over the past funding period include identification of a new therapeutic target in estrogen receptor signaling in breast cancer, advancement of novel isoprenoid anti-cancer compounds into pre-clinical validation studies, and development of RNA-aptamer-based systemic delivery of RNA-interference in prostate cancer. There are numerous past and present productive collaborations both between members of the Program, and with members of other Cancer Center programs. For example, within the program Co-leader Dr. Hohl and Dr. Wiemer have collaborated to develop novel isoprenoid compounds with anti-cancer activity and advance these toward clinical trials and Program Leader Dr. Henry shares separate NCI and NIH grant funding with Drs. Quelle and Lynch, Leaders of the Cancer Genetics and Computational Biology and Cancer Epidemiology programs, respectively and has published recently with Dr. Ballas Leader of the Cancer Immunology and Immunotherapy program. The program consists of 45 members from 7 basic science and 8 clinical departments and 3 Colleges. Peer-reviewed, research funding for this program totals $9.8 million with $3.5 million coming from the NCI. Program members published 339 cancer related papers over the prior funding period. Of these publications, 8% were intraprogrammatic, 27% were interprogrammatic and 2% were both intra and interprogrammatic, for a total of 37% collaborative publications.